{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T23:46:01Z","timestamp":1790725561392,"version":"4.1.0"},"reference-count":49,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2018,2,6]],"date-time":"2018-02-06T00:00:00Z","timestamp":1517875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000191","name":"Kidney Foundation of Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000191","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["Canada Graduate Scholarship-Master\u2019s (CGS M)"],"award-info":[{"award-number":["Canada Graduate Scholarship-Master\u2019s (CGS M)"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Nephrotic syndrome is a kidney disease featured by heavy proteinuria. It is caused by injury to the specialized epithelial cells called \u201cpodocytes\u201d within the filtration unit of the kidney, glomerulus. Previous studies showed that hyperactivation of the RhoGTPase, Rac1, in podocytes causes podocyte injury and glomerulosclerosis (accumulation of extracellular matrix in the glomerulus). However, the mechanism by which Rac1 is activated during podocyte injury is unknown. Trio is a guanine nucleotide exchange factor (GEF) known to activate Rac1. By RNA-sequencing, we found that Trio mRNA is abundantly expressed in cultured human podocytes. Trio mRNA was also significantly upregulated in humans with minimal change disease and focal segmental glomerulosclerosis, two representative causes of nephrotic syndrome. Reduced expression of Trio in cultured human podocytes decreased basal Rac1 activity, cell size, attachment to laminin, and motility. Furthermore, while the pro-fibrotic cytokine, transforming growth factor \u03b21 increased Rac1 activity in control cells, it decreases Rac1 activity in cells with reduced Trio expression. This was likely due to simultaneous activation of the Rac1-GTPase activation protein, CdGAP. Thus, Trio is important in the basal functions of podocytes and may also contribute to glomerular pathology, such as sclerosis, via Rac1 activation.<\/jats:p>","DOI":"10.3390\/ijms19020479","type":"journal-article","created":{"date-parts":[[2018,2,6]],"date-time":"2018-02-06T14:31:17Z","timestamp":1517927477000},"page":"479","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The Role of Trio, a Rho Guanine Nucleotide Exchange Factor, in Glomerular Podocytes"],"prefix":"10.3390","volume":"19","author":[{"given":"Mirela","family":"Maier","sequence":"first","affiliation":[{"name":"Division of Experimental Medicine, McGill University, Montreal, QC H3A 0G4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cindy","family":"Baldwin","sequence":"additional","affiliation":[{"name":"Division of Nephrology, McGill University Health Centre, Montreal, QC H4A 3J1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lamine","family":"Aoudjit","sequence":"additional","affiliation":[{"name":"Division of Nephrology, McGill University Health Centre, Montreal, QC H4A 3J1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Takano","sequence":"additional","affiliation":[{"name":"Division of Experimental Medicine, McGill University, Montreal, QC H3A 0G4, Canada"},{"name":"Division of Nephrology, McGill University Health Centre, Montreal, QC H4A 3J1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,2,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1038\/nrneph.2016.147","article-title":"Minimal change disease and idiopathic FSGS: Manifestations of the same disease","volume":"12","author":"Maas","year":"2016","journal-title":"Nat. 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